title: Additive effects of soluble TWEAK and inflammation on mortality in hemodialysis patients.
abstract: OBJECTIVE
  Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, primarily due to cardiovascular disease. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and CKD.
  
  
  METHODS
  A cross-sectional study was conducted in 218 prevalent patients (121 men; 63 +/- 14 yr) undergoing hemodialysis (HD). sTWEAK levels in relation with the patients' outcome were studied.
  
  
  RESULTS
  sTWEAK plasma levels were 208 [(165 to 272) pg/ml, median interquartile range], significantly lower than healthy controls (P < 0.0001). sTWEAK was negatively associated with inflammatory markers, such as C-reactive protein and IL-6. Overall mortality was assessed after an average follow-up of 31 mo, during which 81 patients died. After controlling for potential confounding variables, patients in the upper tertile of sTWEAK plasma levels had an increased risk of cardiovascular and all-cause mortality. A significant interaction effect between sTWEAK and IL-6 levels was found [synergy index: 2.19 (0.80, 5.93)]. Thus, the association of sTWEAK with mortality was strongest in patients with inflammation (defined as IL-6 > 7.0 pg/ml), in whom high sTWEAK strongly predicted cardiovascular and all-cause mortality. These results were confirmed in a second cohort of HD patients.
  
  
  CONCLUSIONS
  The concurrent presence of elevated sTWEAK plasma concentrations and an inflammatory environment have additive effects on mortality in HD patients. Further studies on the potential different role of sTWEAK in health and disease are warranted.
authors.affiliation: Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Carrero
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Jose L
authors.initials: JL
authors.lastname: Martín-Ventura
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.forename: Olof
authors.initials: O
authors.lastname: Heimbürger
authors.forename: Belén
authors.initials: B
authors.lastname: Marrón
authors.forename: George
authors.initials: G
authors.lastname: Metry
authors.forename: Sunna
authors.initials: S
authors.lastname: Snaedal
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Luis M
authors.initials: LM
authors.lastname: Blanco-Colio
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000401:mortality*; D016022:Case-Control Studies; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D000074049:Cytokine TWEAK; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000401:mortality*; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000401:mortality*; D015203:Reproducibility of Results; D018570:Risk Assessment; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000097:blood*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D000074049:Cytokine TWEAK; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors